title: BRAFV600E: implications for carcinogenesis and molecular therapy.
abstract: The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway is frequently mutated in human cancer. This pathway consists of a small GTP protein of the RAS family that is activated in response to extracellular signaling to recruit a member of the RAF kinase family to the cell membrane. Active RAF signals through MAP/ERK kinase to activate ERK and its downstream effectors to regulate a wide range of biological activities including cell differentiation, proliferation, senescence, and survival. Mutations in the v-raf murine sarcoma viral oncogenes homolog B1 (BRAF) isoform of the RAF kinase or KRAS isoform of the RAS protein are found as activating mutations in approximately 30% of all human cancers. The BRAF pathway has become a target of interest for molecular therapy, with promising results emerging from clinical trials. Here, the role of the most common BRAF mutation BRAF(V600E) in human carcinogenesis is investigated through a review of the literature, with specific focus on its role in melanoma, colorectal, and thyroid cancers and its potential as a therapeutic target.
authors.affiliation: Department of Histopathology, Trinity College, Sir Patrick Dun Research Laboratory, Pathology Building, St. James' Hospital, Dublin 8, Ireland. cantweer@tcd.ie
authors.forename: Emma R
authors.initials: ER
authors.lastname: Cantwell-Dorris
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Leary
authors.forename: Orla M
authors.initials: OM
authors.lastname: Sheils
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*
chemical_list: D048493:Proto-Oncogene Proteins B-raf; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases